This application addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DA-101*: Novel Approaches to Improve Immunogenicity of Vaccine against Small Molecules. The specific aim of this proposal is to provide proof of concept evidence that a newly-developed laser system can significantly augment the production of nicotine-specific antibody (NicAb) elicited by existing nicotine vaccines for a necessary length of time. NicAb induction as an alternative approach to treat tobacco dependence shows great promise in clinical trials, but the efficacy is far from satisfying, owing to insufficient levels of NicAb production even after multiple vaccinations and large variations in the concentration of serum NicAb among vaccinated individuals. We have developed a prototype laser system capable of enhancing and prolonging humoral immune responses, with few side effects, against a model protein antigen, ovalbumin in mice. Our investigation demonstrated that a brief (1~2 mins) illumination of a small area of the skin with a high-repetition, nanosecond pulsed, non-destructive visible light prior immunization enhanced the mobility of antigen presenting cells and their antigen-uptake, boosting humoral immune responses by up to 500% over antigen injection alone. In this proposal, we will test whether this paradigm-breaking approach can significantly enhance and sustain NicAb production provoked by existing nicotine vaccines in both mice and miniature pigs. We will also test potential additive or synergistic effects between laser and alum adjuvants on NicAb production. The laser-based vaccine adjuvant platform under the development is expected to be readily moved to the clinic, because the laser at this setting has been widely used in the clinic for a variety of cosmetic and therapeutic purposes for a decade. This preclinical study will be completed in two years, which, if successful, will not only benefit tobacco dependents, but also open a new avenue to efficiently mount immune responses for other prophylactic and immunotherapeutic vaccines, having a great impact on public health. Induction of nicotine-specific antibody (NicAb) as an alternative approach to treat tobacco dependence shows great promise in clinical trials. Further improvement of the efficacy of nicotine vaccines in treatment of smoking addiction by laser-based adjuvant will have an important impact on public health.